Brief Summary
The purpose of this research is to study the effects of Vitamin D supplementation on the body's response to insulin (a hormone that controls blood sugar), on inflammation, and on specific cells and processes in fat tissue.
Brief Title
Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation
Detailed Description
Over the last several years, studies have shown that low vitamin D levels may increase risk of developing Type 2 Diabetes. The investigators will administer vitamin D3 (cholecalciferol) to non-diabetic, insulin resistant subjects with vitamin D deficiency (total vitamin D levels \<20 ng/ml) to increase the level of vitamin D3. The investigators will study the effects of increased Vitamin D on insulin action, adipose tissue inflammation, and on certain cells and processes in fat tissue.
Investigators will study participants with a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Adipose tissue inflammation will be measured using the following inflammatory markers: IL-6, PAI-1, TNF-alpha, and iNOS.
Investigators will study participants with a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Adipose tissue inflammation will be measured using the following inflammatory markers: IL-6, PAI-1, TNF-alpha, and iNOS.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Insulin Resistance
Eligibility Criteria
Inclusion Criteria:
* Serum 25(OH)D\<20ng/ml
* Insulin Resistant based on HOMA-IR score of \>3
* Able and willing to provide informed consent
* BMI 20-35
Exclusion Criteria:
* HIV/AIDS
* History of any cancer
* Sarcoidosis
* Alcohol or substance abuse
* Cushing's syndrome
* Primary hyperparathyroidism
* Nephrolithiasis
* Pregnancy or breastfeeding
* Regular visits to a tanning salon
* Hypercalcemia or hypocalcemia
* Untreated or uncontrolled hypertension
* Any chronic illness requiring medication, other than arthritis, hypertension and hyperlipidemia
* Serum 25(OH)D\<20ng/ml
* Insulin Resistant based on HOMA-IR score of \>3
* Able and willing to provide informed consent
* BMI 20-35
Exclusion Criteria:
* HIV/AIDS
* History of any cancer
* Sarcoidosis
* Alcohol or substance abuse
* Cushing's syndrome
* Primary hyperparathyroidism
* Nephrolithiasis
* Pregnancy or breastfeeding
* Regular visits to a tanning salon
* Hypercalcemia or hypocalcemia
* Untreated or uncontrolled hypertension
* Any chronic illness requiring medication, other than arthritis, hypertension and hyperlipidemia
Inclusion Criteria
Inclusion Criteria:
* Serum 25(OH)D\<20ng/ml
* Insulin Resistant based on HOMA-IR score of \>3
* Able and willing to provide informed consent
* BMI 20-35
* Serum 25(OH)D\<20ng/ml
* Insulin Resistant based on HOMA-IR score of \>3
* Able and willing to provide informed consent
* BMI 20-35
Gender
All
Gender Based
false
Keywords
Glucose Metabolism Disorders
Insulin Resistance
Endocrine System
Vitamin D
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
21 Years
NCT Id
NCT01354964
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2008-225
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation
Primary Outcomes
Outcome Description
Endogenous glucose production (EGP) was assessed at each study visit to evaluate hepatic insulin sensitivity. Percent change between the EGP at baseline and second visit (after treatment for up to 3 months with Vitamin D to reach a target level of ≥30 ng/ml), and baseline and third visits (after treatment for up to 6 months with Vitamin D in order to reach a target level of ≥50 ng/ml) will be calculated.
Outcome Measure
Percent Change in Hepatic Insulin Sensitivity
Outcome Time Frame
2nd clamp visit (after up to 3 months) and 3rd clamp visit (after up to 6 months)
Secondary Ids
Secondary Id
5K23RR023335-02
Secondary Outcomes
Outcome Description
The rate of glucose uptake to determine peripheral insulin sensitivity was measured using the rate of disappearance (Rd) of glucose at each study visit. Percent change between the Rd at baseline and second visit (after treatment with Vitamin D for up to 3 months to target level of ≥30 ng/ml), and baseline and third visits (after treatment with Vitamin D for up to 6 months to target level of ≥50 ng/ml) will be calculated.
Outcome Time Frame
2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Outcome Measure
Percent Change in Peripheral Glucose Uptake
Outcome Description
Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. TNF-α gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes \[HKGs\]) as a ratio, which is a measure of relative gene expression.
Outcome Time Frame
2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Outcome Measure
Evaluated Expression of Pro-inflammatory Gene TNF-α
Outcome Description
Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. IL-6 gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes \[HKGs\]) as a ratio, which is a measure of relative gene expression.
Outcome Time Frame
2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Outcome Measure
Evaluated Expression of Pro-inflammatory Gene IL-6
Outcome Description
Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. iNOS gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes \[HKGs\]) as a ratio, which is a measure of relative gene expression.
Outcome Time Frame
2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Outcome Measure
Evaluated Expression of Pro-inflammatory Gene iNOS
Outcome Description
Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. PAI-1 gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes \[HKGs\]) as a ratio, which is a measure of relative gene expression.
Outcome Time Frame
2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Outcome Measure
Evaluated Expression of Pro-inflammatory Gene PAI-1
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
21
Investigators
Investigator Type
Principal Investigator
Investigator Name
Meredith Hawkins
Investigator Email
meredith.hawkins@einsteinmed.org
Investigator Phone
718-430-3186